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A BAFF/APRIL axis regulates obesogenic diet-driven weight gain.

ABSTRACT: The impact of immune mediators on weight homeostasis remains underdefined. Interrogation of resistance to diet-induced obesity in mice lacking a negative regulator of Toll-like receptor signaling serendipitously uncovered a role for B cell activating factor (BAFF). Here we show that overexpression of BAFF in multiple mouse models associates with protection from weight gain, approximating a log-linear dose response relation to BAFF concentrations. Gene expression analysis of BAFF-stimulated subcutaneous white adipocytes unveils upregulation of lipid metabolism pathways, with BAFF inducing white adipose tissue (WAT) lipolysis. Brown adipose tissue (BAT) from BAFF-overexpressing mice exhibits increased Ucp1 expression and BAFF promotes brown adipocyte respiration and in vivo energy expenditure. A proliferation-inducing ligand (APRIL), a BAFF homolog, similarly modulates WAT and BAT lipid handling. Genetic deletion of both BAFF and APRIL augments diet-induced obesity. Lastly, BAFF/APRIL effects are conserved in human adipocytes and higher BAFF/APRIL levels correlate with greater BMI decrease after bariatric surgery. Together, the BAFF/APRIL axis is a multifaceted immune regulator of weight gain and adipose tissue function.

SUBMITTER: Chan CC

PROVIDER: S-EPMC8131685 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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A BAFF/APRIL axis regulates obesogenic diet-driven weight gain.

Chan Calvin C CC Harley Isaac T W ITW Pfluger Paul T PT Trompette Aurelien A Stankiewicz Traci E TE Allen Jessica L JL Moreno-Fernandez Maria E ME Damen Michelle S M A MSMA Oates Jarren R JR Alarcon Pablo C PC Doll Jessica R JR Flick Matthew J MJ Flick Leah M LM Sanchez-Gurmaches Joan J Mukherjee Rajib R Karns Rebekah R Helmrath Michael M Inge Thomas H TH Weisberg Stuart P SP Pamp Sünje J SJ Relman David A DA Seeley Randy J RJ Tschöp Matthias H MH Karp Christopher L CL Divanovic Senad S

Nature communications 20210518 1

The impact of immune mediators on weight homeostasis remains underdefined. Interrogation of resistance to diet-induced obesity in mice lacking a negative regulator of Toll-like receptor signaling serendipitously uncovered a role for B cell activating factor (BAFF). Here we show that overexpression of BAFF in multiple mouse models associates with protection from weight gain, approximating a log-linear dose response relation to BAFF concentrations. Gene expression analysis of BAFF-stimulated subcu ...[more]

PMID: 34006859

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Project description:ObjectiveTo determine whether selected features of the built environment can predict weight gain in a large longitudinal cohort of adults.MethodsWeight trajectories over a 5-year period were obtained from electronic health records for 115,260 insured patients aged 18-64 years in the Kaiser Permanente Washington health care system. Home addresses were geocoded using ArcGIS. Built environment variables were population, residential unit, and road intersection densities captured using Euclidean-based SmartMaps at 800-m buffers. Counts of area supermarkets and fast food restaurants were obtained using network-based SmartMaps at 1600, and 5000-m buffers. Property values were a measure of socioeconomic status. Linear mixed effects models tested whether built environment variables at baseline were associated with long-term weight gain, adjusting for sex, age, race/ethnicity, Medicaid insurance, body weight, and residential property values.ResultsBuilt environment variables at baseline were associated with differences in baseline obesity prevalence and body mass index but had limited impact on weight trajectories. Mean weight gain for the full cohort was 0.06 kg at 1 year (95% CI: 0.03, 0.10); 0.64 kg at 3 years (95% CI: 0.59, 0.68), and 0.95 kg at 5 years (95% CI: 0.90, 1.00). In adjusted regression models, the top tertile of density metrics and frequency counts were associated with lower weight gain at 5-years follow-up compared to the bottom tertiles, though the mean differences in weight change for each follow-up year (1, 3, and 5) did not exceed 0.5 kg.ConclusionsBuilt environment variables that were associated with higher obesity prevalence at baseline had limited independent obesogenic power with respect to weight gain over time. Residential unit density had the strongest negative association with weight gain. Future work on the influence of built environment variables on health should also examine social context, including residential segregation and residential mobility.

Dataset Information

A BAFF/APRIL axis regulates obesogenic diet-driven weight gain.

Publications

A BAFF/APRIL axis regulates obesogenic diet-driven weight gain.

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